rs10883969 (SFR1): Preeclampsia Candidate Variant
Key takeaways
- rs10883969, near the SFR1 gene, was identified as a suggestive candidate SNP for preeclampsia in a multi-ethnic genome-wide association study, but did not reach genome-wide significance.
- Evidence comes from a single GWAS with small case numbers across three ethnic groups (21 to 62 cases per group); the original authors called for further replication.
- GTEx v11 data link this variant to reduced expression of CFAP43 in tibial nerve and transverse colon, and to increased expression of ITPRIP-AS1 across three basal ganglia brain regions.
- The same variant has opposing effects on GSTO2 depending on tissue: increased expression in the cerebellar hemisphere, but reduced expression in both sun-exposed and non-sun-exposed skin.
- The preeclampsia association is preliminary; no genome-wide significant replication evidence appears in the provided sources.
Key takeaways
- rs10883969, near the SFR1 gene, was identified as a suggestive candidate SNP for preeclampsia in a multi-ethnic genome-wide association study, but did not reach genome-wide significance.
- Evidence comes from a single GWAS with small case numbers across three ethnic groups (21 to 62 cases per group); the original authors called for further replication.
- GTEx v11 data link this variant to reduced expression of CFAP43 in tibial nerve and transverse colon, and to increased expression of ITPRIP-AS1 across three basal ganglia brain regions.
- The same variant has opposing effects on GSTO2 depending on tissue: increased expression in the cerebellar hemisphere, but reduced expression in both sun-exposed and non-sun-exposed skin.
- The preeclampsia association is preliminary; no genome-wide significant replication evidence appears in the provided sources.
What the research says A genome-wide association study (GWAS) of preeclampsia drew on HAPO study data from mothers of Afro-Caribbean (21 cases, 1,049 controls), Hispanic (62 cases, 661 controls), and European ancestry (50 cases, 1,207 controls), identifying top candidate SNPs including variants near SFR1; none reached Bonferroni-corrected genome-wide significance, and suggestive replication in the SOPHIA cohort (177 preeclampsia cases, 116 Caucasian controls) led the authors to characterize all findings as novel candidates warranting further investigation. Separately, GTEx v11 data linking genetic variants to gene expression levels (953 donors, cis-window, FDR<0.05) show that the alternate allele at this locus is associated with altered expression of three nearby genes - CFAP43, ITPRIP-AS1, and GSTO2 - across brain, nerve, colon, and skin tissues GTEx Portal.
Reported associations
- Preeclampsia (suggestive, not genome-wide significant): Identified as a top candidate SNP in a multi-ethnic GWAS of Afro-Caribbean (21 cases, 1,049 controls), Hispanic (62 cases, 661 controls), and European ancestry (50 cases, 1,207 controls) mothers from the HAPO cohort; suggestively replicated in the SOPHIA cohort (177 cases, 116 controls). No specific effect size for this variant was included in the available study text.
- CFAP43 expression - tibial nerve and transverse colon: Alternate allele associated with reduced CFAP43 expression in tibial nerve (p=2.6e-15) and transverse colon (p=3.2e-10) GTEx Portal.
- ITPRIP-AS1 expression - basal ganglia: Alternate allele associated with increased ITPRIP-AS1 expression in putamen (p=1.1e-8), caudate nucleus (p=2.3e-9), and nucleus accumbens (p=1.8e-8) GTEx Portal.
- GSTO2 expression - opposing tissue-specific effects: Alternate allele associated with increased GSTO2 expression in the cerebellar hemisphere (p=6.1e-8), but reduced expression in sun-exposed lower leg skin (p=8.1e-17) and non-sun-exposed suprapubic skin (p=5.1e-11) GTEx Portal.
Evidence quality The preeclampsia association rests on a single GWAS with notably small case samples: 21 Afro-Caribbean cases, 62 Hispanic cases, and 50 European ancestry cases. No SNP in the study reached Bonferroni-corrected genome-wide significance, and the authors explicitly described their findings as novel candidate variants that warrant further replication and investigation. Replication in SOPHIA (177 cases, 116 controls) was described as suggestive for several variants, but no specific statistics for rs10883969 were included in the available study text. The gene expression associations from GTEx v11 are statistically robust - the CFAP43 tibial nerve signal reaches p=2.6e-15 - but these reflect gene-regulatory mechanisms and do not establish a causal role in disease. Overall, the preeclampsia evidence is preliminary and the available sources include no large-scale independent replication.
Tissue-specific expression effects
- CFAP43: The alternate allele is associated with reduced expression in tibial nerve and transverse colon GTEx Portal.
- ITPRIP-AS1: The alternate allele is associated with increased expression in three basal ganglia subregions: putamen, caudate nucleus, and nucleus accumbens GTEx Portal.
- GSTO2: The alternate allele is associated with increased expression in the cerebellar hemisphere but reduced expression in both sun-exposed and non-sun-exposed skin, a directionally opposing pattern across tissues GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10883969 and which gene is it near?
rs10883969 is a single nucleotide polymorphism (a one-letter change in the genetic code) located near the SFR1 gene. It was identified as a candidate variant in a genome-wide association study of preeclampsia, a hypertensive complication of pregnancy.
Is rs10883969 definitively linked to preeclampsia?
No. It appeared among the top candidate SNPs in a preeclampsia GWAS, but did not reach the stringent statistical threshold required for genome-wide significance. The authors explicitly stated the finding needs further replication before conclusions can be drawn.
What do GTEx data show for rs10883969?
GTEx v11 data show the alternate allele is associated with reduced expression of CFAP43 in tibial nerve and colon, increased expression of ITPRIP-AS1 in three basal ganglia brain regions, and opposing effects on GSTO2 - increased in the cerebellum and reduced in skin. These are gene regulation associations, not direct disease outcomes.
Which ethnic groups were studied for the preeclampsia association?
The GWAS used HAPO study data from mothers of Afro-Caribbean, Hispanic, and European ancestry, with a separate replication attempt in a Caucasian cohort from the SOPHIA study.
How strong is the evidence for rs10883969 as a preeclampsia risk variant?
The evidence is preliminary. The study reported suggestive but not genome-wide significant findings, case numbers were small (21 to 62 per ethnic group), and no large-scale independent replication has been reported in the provided sources.